Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat

Abstract

Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug's dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized. The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults. CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (n = 34) and adult (n = 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots. Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA. Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.